The project includes two parts: 1) Mutations in RecQ-helicase genes associate with autosomal recessive premature aging disorders, often characterized with genome instability and telomere attrition. We are collaborating with Dr. Vilhelm Bohr laboratory examining the role of RecQ helicases in telomere length regulation in human cells. Our studies illustrate that human premature aging disorder with RecQ4 deficiency has telomere replication defects. 2) We have screened for helicase-like proteins that associate with telomeres binding proteins, namely TRF1, TRF2, and POT1 by dual-tag based affinity purification in combination with tandem mass spectrometry approach. Several putative associating partners identified for each of three binding proteins fell into categories such as DNA damage repair and helicase like proteins. We plan to further verify these putative proteins and their roles in telomeres. These studies will unveil potential novel mechanism(s) of how helicases may impact telomere integrity and thus age-related diseases.